EF-M2 (Immutalon) macrophage glyco-modulation for activity and vitality in aging companion dogs (GERI-VITAL-DOG)
GERI-VITAL-DOG was a multicenter, randomized, double-blind, placebo-controlled trial at two referral clinics in Novosibirsk, Russia that randomized 60 client-owned geriatric dogs (10 years or older, mean 12.4 years) 1:1 to subcutaneous EF-M2 (Immutalon) at 0.1 ug/kg every 72 h for 4 weeks, with a blinded step-up to every 48 h for partial responders, or matched placebo, followed by 4 weeks off treatment. The co-primary endpoints were accelerometer-measured active minutes per day at week 1 and a day-28 vitality composite. EF-M2 beat placebo on both (+23.05 min/day; +2.01 z-units), with favorable secondaries and owner-reported global improvement of 93.3% vs 10.0% at day 28, and mild infrequent adverse events; the product and unrestricted funding came from Activator MAF, LLC.
Record
| Design | randomized controlled trial |
|---|---|
| Status | completed |
| Setting | client owned |
| Intervention | Subcutaneous EF-M2 (Immutalon), a GcMAF-derived protein for macrophage-targeted glyco-modulation |
| Intervention class | drug |
| Comparator | Matched placebo (identical 0.9% sodium chloride vehicle, mirror injections and mirror step-up) |
| Dose regimen | 0.1 ug/kg (0.1 mL/kg) subcutaneously every 72 h for 4 weeks, with protocolized blinded step-up to every 48 h at day 14 for partial responders; followed by 4 weeks off-treatment |
| Duration | 4 weeks of treatment plus 4 weeks off-treatment (assessments to day 56) |
| Dogs | 60 |
| Population note | 60 randomized (30 EF-M2; 30 placebo), intention-to-treat population |
| Age | >= 10 years; mean age 12.4 +/- 1.8 y |
| Other | client-owned geriatric dogs, clinically stable, at two referral veterinary clinics in Novosibirsk, Russia |
| Primary outcome | Co-primary endpoints tested hierarchically: change in accelerometer-measured active minutes/day at week 1 and change in a day-28 vitality composite (z-score of inverted CBPI-PSS, HRQL-vitality and appetite VAS) |
| Result (as reported) | EF-M2 was superior to placebo on both co-primary endpoints: +23.05 min/day at week 1 (95% CI, 18.16-27.94; p < 0.001) and +2.01 z-units at day 28 (95% CI, 1.52-2.50; p < 0.001). Key secondaries favored EF-M2, including greater week-4 activity (+33.00 min/day), lower BAER auditory threshold (-5.28 dB) and reduced transepidermal water loss. Owner-reported global improvement was 93.3% vs 10.0% at day 28 and 50.0% vs 16.7% at day 56 off-treatment. Adverse events were infrequent, mild and similar to placebo. |
| Lead organisation | Center for New Medical Technologies (Novosibirsk, Russia) and Triangel Scientific Research Laboratory (San Francisco, CA, USA); conducted at VEGA Veterinary Clinic and BALTO Veterinary Clinic, Novosibirsk |
| Sponsor or funder | Activator MAF, LLC (Novosibirsk, Russia): supplied Immutalon and provided unrestricted financial support |
| Tags | drug, immunomodulation, macrophage, activity, vitality, inflammaging, client-owned |
Notes: No trial registration is mentioned; clinic IACUC approvals are dated January 2025 and the protocol version is dated November 2024. The abstract renders the dose as 0.1 μg/kg; the full text uses the micro sign in 1 µg/mL.
Sources and verbatim quotes
Precision Glyco-Modulation of Macrophages with EF-M2 (Immutalon<sup>TM</sup>) Improves Function and Lowers Inflammatory Biomarkers in Aging Dogs: A Double-Blind, Placebo-Controlled Trial. (2025) PMID 41472148 (results)
We evaluated whether macrophage-targeted glyco-modulation can improve day-to-day function in aging companion animals.
In a multicenter, randomized, double-blind, placebo-controlled trial, 60 client-owned geriatric dogs (≥10 years) received subcutaneous EF-M2 (0.1 μg/kg, every 72 h for 4 weeks; protocolized, blinded step-up to every 48 h at day 14 for partial responders) or matched placebo, followed by 4 weeks off-treatment.
Two prespecified co-primary endpoints were tested hierarchically: change in accelerometer-measured active minutes/day at week 1 and change in a day-28 vitality composite (z-score of inverted CBPI-PSS, HRQL-vitality, and appetite VAS).
EF-M2 was superior to placebo on both: +23.05 min/day at week 1 (95% CI, 18.16-27.94;
) and +2.01 z-units at day 28 (95% CI, 1.52-2.50;
Key secondaries favored EF-M2, including greater week-4 activity (+33.00 min/day, 26.83-39.18;
lower BAER auditory threshold (-5.28 dB, -7.53 to -3.04;
Owner-reported global improvement was more frequent with EF-M2 at day 28 (93.3% vs. 10.0%) and remained higher at day 56 off-treatment (50.0% vs. 16.7%).
Adverse events were infrequent, mild, and similar to placebo; no treatment-related withdrawals or serious events occurred.
These findings support macrophage-targeted glyco-modulation as a promising approach to rapidly improve real-world activity and multidomain vitality in older dogs, with short-term signals persisting off-treatment; longer, adequately powered trials are warranted to define durability, structural outcomes, and phenotype-specific benefits.
Precision Glyco-Modulation of Macrophages with EF-M2 (Immutalon<sup>TM</sup>) Improves Function and Lowers Inflammatory Biomarkers in Aging Dogs: A Double-Blind, Placebo-Controlled Trial. (2025) PMID 41472148 (design)
GERI-VITAL-DOG was a multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial in geriatric dogs (1:1 allocation).
The trial was conducted at two referral veterinary clinics for companion animals. All study operations (design finalization, conduct, monitoring, data management, and statistical analysis) were performed independently by investigators from the Center for New Medical Technologies (Novosibirsk, Russia) and the Triangel Scientific Research Laboratory (San Francisco, CA, USA).
Client-owned dogs aged ≥10 years were eligible if clinically stable and if owners consented to have the dog wear an accelerometer for ≥20 h/day.
was supplied as a sterile, preservative-free aqueous solution of GcMAF-derived EF-M2 protein (1 µg/mL) in 0.9% sodium chloride (normal saline) in 1 mL Type I glass vials.
The placebo consisted of the identical vehicle (0.9% sodium chloride) without EF-M2, filled into visually indistinguishable vials and administered at the same volume per kilogram and on a schedule mirrored to that of the active regimen, including the protocolized step-up.
was reviewed and approved by the Institutional Animal Care and Use Committees of both participating veterinary clinics: VEGA Veterinary Clinic, Novosibirsk (protocol VEGA-VCA-2025-014, approved 28 January 2025) and BALTO Veterinary Clinic, Novosibirsk (protocol BALTO-VCB-2025-021, approved 29 January 2025).
Activator MAF, LLC (Novosibirsk, Russia) supplied Immutalon^TM^ and provided unrestricted financial support.
Sixty geriatric dogs were randomized (30 EF-M2; 30 placebo) and comprised the intention-to-treat (ITT) population for all efficacy analyses.
Mean age was 12.4 ± 1.8 y, baseline objective activity averaged 144.8 ± 38.3 min/day, and distributions of sex, neuter status, and symptom flags (pain, pruritus, otitis) were comparable between groups (Table 1).
Reproduce: canine_trial_search(trial_id="ef-m2-immutalon-geri-vital-dog-rct-2025") in dog-geroscience-mcp; dataset canine-trial-registry.